Changes in peritoneal myeloid populations and their proinflammatory cytokine expression during infection with Listeria monocytogenes are altered in the absence of gamma/delta T cells

Evidence that gamma/delta T cells play a broad, immunoregulatory role has been accumulating steadily. We show here that myeloid cells are disregulated after peritoneal infection with Listeria monocytogenes in mice lacking gamma/delta T cells. Inflammatory populations of neutrophils and monocytes recruited to the site of infection remained longer. Intracellular cytokine analysis showed that frequencies of myeloid cells producing interleukin-12 and tumor necrosis factor alpha were higher and remained elevated longer after infection in mice genetically deficient in gamma/delta T cells. In vivo dye-tracking studies indicated that the majority of inflammatory monocytes differentiated into resident tissue macrophages in situ. In vitro experiments confirmed that monocytes harvested from mice lacking gamma/delta T cells were defective in their maturation process. This evidence suggests that gamma/delta T cells promote differentiation in the monocyte/macrophage lineage. These cells are important for bactericidal activity, inflammatory cytokine production, clearance of inflammatory neutrophils, and ultimately, antigen presentation to T cells. Regulation of monocyte/macrophage differentiation may underlie a broad segment of the phenotypic alterations that have been reported in mice lacking gamma/delta T cells.     

Blood and Marrow Transplant Clinical Trials Network State of the Science Symposium 2007.

Outcomes of hematopoietic cell transplantation are steadily improving. New techniques have reduced transplant toxicities, and there are new sources of hematopoietic stem cells from unrelated donors. In June 2007 the Blood and Marrow Transplant Clinical Trials Network convened a State of the Science Symposium of more than 200 participants in Ann Arbor to identify the most compelling clinical research opportunities in the field. This report summarizes the symposium's discussions and identifies eleven high priority clinical trials that the network plans to pursue over the course of the next several years.     

Genomic screen for loci associated with alcohol dependence in Mission Indians.

Alcohol dependence is a leading cause of morbidity and mortality in Native Americans, yet biological factors underlying the disorder in this ethnic group remain elusive. This study's aims were to map susceptibility loci for DSM-III-R alcohol dependence and two narrower alcohol-related phenotypes in Mission Indian families. Each participant gave a blood sample and completed an interview using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) that was used to make alcohol dependence diagnoses and the narrower phenotypes of withdrawal, and drinking severity. Genotypes were determined for a panel 791 microsatellite polymorphisms. Analyses of multipoint variance component LOD scores for the dichotomous DSM-III-R phenotype revealed no peak LOD scores that exceeded 2.0 at any chromosome location. Two chromosomes, 4 and 12, had peak LOD scores that exceeded 2 for the alcohol use severity phenotype and three chromosomes 6, 15, 16 were found to have peaks with LOD scores that exceeded 2 for the withdrawal phenotype. Evidence for linkage to chromosomes 4 and 15, and 16 have been reported previously for alcohol related phenotypes whereas no evidence has as yet been reported for chromosomes 6 and 12. Combined linkage and association analysis suggest that alcohol dehydrogenase 1B gene polymorphisms are partially responsible for the linkage result on chromosome 4 in this population. These results corroborate the importance of several chromosomal regions highlighted in prior segregation studies in alcoholism and further identify new regions of the genome that may be unique to either the restricted phenotypes evaluated or this population of Mission Indians.     

Twice weekly prophylactic therapy in haemophilia A.

Factor VIII-containing materials were administered to four severely affected haemophiliacs twice weekly in doses calculated to raise the factor VIII level to either 15% or 30% of average normal. The pooled results from those patients with statistically similar baseline bleeding frequencies showed a significant reduction in bleeding frequency on both doses in the first 48 hours. The 30% dose produced a more significant reduction than the 15% dose in the first 24 hours, but there was no significant difference between the two doses in the second 24 hours. It appears that to reduce the bleeding frequency of severely affected haemophiliacs by 60% would require a two-and-a-half-fold increase in therapeutic materials. A 90% reduction would need nine times the amount of material currently in use.     

Effect of magnesium on sodium transport in toad urinary bladder.

Voltage-clamp techniques were employed to examine the effect of magnesium (Mg) on sodium transport in the isolated urinary bladder of the Dominican toad. Substitution of 1 mM Mg had no effect, but 3-mM Mg substitution resulted in a reversible increase in short-circuit current (27%) and potential difference (19%) and decrease in transepithelial resistance (14%); no greater effect was seen with 5- or 10-mM Mg substitution. The effect was produced by mucosal or mucosal and serosal Mg substitution; serosal Mg substitution was without effect. Analysis of electrical parameters disclosed that magnesium increased net sodium transport via an effect on the sodium pump.     

The histologic border zone of acute myocardial infarction--islands or peninsulas?

Observation of isolated islands of apparently surviving myocardium within areas of necrotic tissue at the edge of myocardial infarctions has been interpreted by some as histologic evidence of a unique "border zone" region. Serial section reconstruction of transmural canine myocardial infarctions was performed in this study to establish whether these islands were truly isolated or were continuous peninsulas of tissue separated by the plane of section. Three-dimensional analysis of the infarcts revealed no true islands but instead demonstrated a region composed of highly complex interdigitating peninsulas. We conclude that there is an extremely irregular but sharp boundary demarcating normal and infarcted myocardium with no intermediate zone. This observation is discussed in relation to recent data, based on coronary blood flow and creatine phosphokinase analysis, which also demonstrates a sharp boundary between the normal and infarct zones.     

The development of a Pharmacy Student Work Values Inventory (PSWVI).

The purpose of this study was to develop an instrument that measures pharmacy student work values. The instrument was included in a questionnaire mailed to 1,820 pharmacy students who had just graduated or were in their last year of pharmacy school from 19 schools of pharmacy nationwide. A total of 738 questionnaires were deemed usable for a usable rate of 41.5 percent. After Varimax factor analysis, eleven reliable factors emerged: Quality Patient Care; Supervision and Company Policy; Work Creativity/Variety; Status; Management/Leadership; Economic Return; Work Schedule; Family Responsibilities; Job Security; Co-worker Relationships; and Policies and Procedures. "Job Security," "Family Responsibilities," and "Patient Care" were rated least and negatively important respectively. There were no differences between BS and PharmD degree aspirants on the eleven factors; however, there were some significant differences between sexes. Women rated "Supervision and Company Policy" and "Quality Patient Care" higher than men. Men did not negatively value "Work Schedule" as much as women did, i.e., women preferred to work traditional, weekday hours.     

Mental Health Screening Practices Among Primary Care Providers in High HIV Burden Areas of the South: Does Having Patients with HIV Matter?

The Journal of Behavioral Health Services & Research - Mental health (MH) disorders are associated with HIV-related risk and health outcomes. Primary care providers (PCPs) conducting MH...     

Development and evaluation of an internally controlled semiautomated PCR assay for quantification of cell-free cytomegalovirus

Quantification of circulating human cytomegalovirus (HCMV) is useful in clinical contexts such as virological surveillance of bone marrow transplant recipients and monitoring of antiviral therapy. This report describes an internally controlled, quantitative, semiautomated, HCMV genome assay that was developed primarily to measure HCMV DNA in the plasma of severely leucopaenic patients. It exhibits greater sensitivity, wider dynamic range and higher sample throughput than a number of previously described commercial and "in-house" assays. Viral DNA extraction from EDTA plasma samples was automated using a BioRobot 9604 (Qiagen). HCMV strain AD169 was used to prepare a calibration curve and murine cytomegalovirus (MCMV) strain Smith was added as internal control to all calibration standards and test samples. Amplification was performed using a set of primers based on the HCMV UL50 region, capable of amplifying both human and murine CMV. The yield of biotinylated polymerase chain reaction (PCR) products was estimated using HCMV-specific and MCMV-specific enzyme-labelled probes and automated chemiluminescence detection. Log-transformed HCMV-to-MCMV signal ratios were calculated and used for quantification of test samples against simultaneously extracted MCMV-spiked calibration standards. Evaluation of the assay sensitivity by Probit analysis demonstrated a 95% probability of detection at 100 HCMV genomes per ml of plasma; the dynamic range was shown to be > or = 4 log(10). A total of 315 samples from 61 bone marrow transplant patients were analysed by both the quantitative PCR (qPCR) and by a previously validated nested nonquantitative PCR (NQPCR). A high level of concordance (90%) was observed between the two assays, although the qPCR assay exhibited slightly greater sensitivity.